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Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis

Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate imm...

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Autores principales: Hernández-Beeftink, Tamara, Guillen-Guio, Beatriz, Rodríguez-Pérez, Héctor, Marcelino-Rodríguez, Itahisa, Lorenzo-Salazar, Jose M., Corrales, Almudena, Prieto-González, Miryam, Rodríguez-Pérez, Aurelio, Carriedo, Demetrio, Blanco, Jesús, Ambrós, Alfonso, González-Higueras, Elena, Casanova, Nancy G., González-Garay, Manuel, Espinosa, Elena, Muriel, Arturo, Domínguez, David, de Lorenzo, Abelardo García, Añón, José M., Soro, Marina, Belda, Javier, Garcia, Joe G. N., Villar, Jesús, Flores, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453061/
https://www.ncbi.nlm.nih.gov/pubmed/34557198
http://dx.doi.org/10.3389/fimmu.2021.737369
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author Hernández-Beeftink, Tamara
Guillen-Guio, Beatriz
Rodríguez-Pérez, Héctor
Marcelino-Rodríguez, Itahisa
Lorenzo-Salazar, Jose M.
Corrales, Almudena
Prieto-González, Miryam
Rodríguez-Pérez, Aurelio
Carriedo, Demetrio
Blanco, Jesús
Ambrós, Alfonso
González-Higueras, Elena
Casanova, Nancy G.
González-Garay, Manuel
Espinosa, Elena
Muriel, Arturo
Domínguez, David
de Lorenzo, Abelardo García
Añón, José M.
Soro, Marina
Belda, Javier
Garcia, Joe G. N.
Villar, Jesús
Flores, Carlos
author_facet Hernández-Beeftink, Tamara
Guillen-Guio, Beatriz
Rodríguez-Pérez, Héctor
Marcelino-Rodríguez, Itahisa
Lorenzo-Salazar, Jose M.
Corrales, Almudena
Prieto-González, Miryam
Rodríguez-Pérez, Aurelio
Carriedo, Demetrio
Blanco, Jesús
Ambrós, Alfonso
González-Higueras, Elena
Casanova, Nancy G.
González-Garay, Manuel
Espinosa, Elena
Muriel, Arturo
Domínguez, David
de Lorenzo, Abelardo García
Añón, José M.
Soro, Marina
Belda, Javier
Garcia, Joe G. N.
Villar, Jesús
Flores, Carlos
author_sort Hernández-Beeftink, Tamara
collection PubMed
description Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39–9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS.
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spelling pubmed-84530612021-09-22 Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis Hernández-Beeftink, Tamara Guillen-Guio, Beatriz Rodríguez-Pérez, Héctor Marcelino-Rodríguez, Itahisa Lorenzo-Salazar, Jose M. Corrales, Almudena Prieto-González, Miryam Rodríguez-Pérez, Aurelio Carriedo, Demetrio Blanco, Jesús Ambrós, Alfonso González-Higueras, Elena Casanova, Nancy G. González-Garay, Manuel Espinosa, Elena Muriel, Arturo Domínguez, David de Lorenzo, Abelardo García Añón, José M. Soro, Marina Belda, Javier Garcia, Joe G. N. Villar, Jesús Flores, Carlos Front Immunol Immunology Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39–9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS. Frontiers Media S.A. 2021-09-07 /pmc/articles/PMC8453061/ /pubmed/34557198 http://dx.doi.org/10.3389/fimmu.2021.737369 Text en Copyright © 2021 Hernández-Beeftink, Guillen-Guio, Rodríguez-Pérez, Marcelino-Rodríguez, Lorenzo-Salazar, Corrales, Prieto-González, Rodríguez-Pérez, Carriedo, Blanco, Ambrós, González-Higueras, Casanova, González-Garay, Espinosa, Muriel, Domínguez, de Lorenzo, Añón, Soro, Belda, Garcia, Villar and Flores https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hernández-Beeftink, Tamara
Guillen-Guio, Beatriz
Rodríguez-Pérez, Héctor
Marcelino-Rodríguez, Itahisa
Lorenzo-Salazar, Jose M.
Corrales, Almudena
Prieto-González, Miryam
Rodríguez-Pérez, Aurelio
Carriedo, Demetrio
Blanco, Jesús
Ambrós, Alfonso
González-Higueras, Elena
Casanova, Nancy G.
González-Garay, Manuel
Espinosa, Elena
Muriel, Arturo
Domínguez, David
de Lorenzo, Abelardo García
Añón, José M.
Soro, Marina
Belda, Javier
Garcia, Joe G. N.
Villar, Jesús
Flores, Carlos
Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis
title Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis
title_full Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis
title_fullStr Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis
title_full_unstemmed Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis
title_short Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis
title_sort whole-blood mitochondrial dna copies are associated with the prognosis of acute respiratory distress syndrome after sepsis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453061/
https://www.ncbi.nlm.nih.gov/pubmed/34557198
http://dx.doi.org/10.3389/fimmu.2021.737369
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